Hepatitis C virus is a significant public health issue and its clinical outcomes are variable. Host virus interactions play important roles in disease and treatment outcomes but the underlying Immunological mechanisms leading to spontaneous or treatment associated viral clearance are not welt understood. The studies proposed within this Hepatitis C Cooperative Research Center (HC CRC) application are focused on the innate immune mechanisms of HCV control. The proposed studies within all three projects Include both translational investigation using clinical specimens from patients with chronic hepatitis C, and in vitro expenments to evaluate mechanisms of HCV innate immune triggering, response, and infection control. These studies will rely on specialized human liver tissues, sera, plasma samples, and the associated clinical Information. Thus, we propose to establish a Clinical Core for service to all three projects in this HC CRC Program, The Liver Center at Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, is a major tertiary referral center in the Boston region and will be able to meet the requirements of the Clinical Core. The Clinical Core will serve as a central platform for the global studies in the U19 Program by providing clinical expertise and well characterized clinical specimens in support of investigating the hypotheses within each individual project of this HC CRC.